Somatic stem cells have been proposed for various therapeutic applications, including, for example, in animal models of cell replenishment therapy. The therapeutic potential of grafted stem cells can only be translated to clinical use if an ethically acceptable source of autologous stem cells is available, and if control of self renewal and fate decisions that program stem cell maturation into specific cell types is achieved.
A number of studies have described differentiation of embryonic stem cells down the hepatocyte lineage (see, e.g., Sharma, N. S. et al., Biotechnology & Bioengineering, 94 (6): 1053-93 (2006); Maguire, T., et al., Biotechnology & Bioengineering, 93(3):581-591 (2006) and Chen Y, et al., Cell Transplant. 2006; 15(10):865-71). In addition, human bone marrow derived mesenchymal cells were examined for the capacity to differentiate into functioning hepatocytes with some success (Ong S Y, Dai H, Leong K W, Tissue Eng. 2006 Oct. 1; Ong S Y, Dai H, Leong K W Biomaterials (22):4087-97 (2006) (epub Apr. 17, 2006); Sato Y, Araki H, Kato J, Nakamura K, Blood. 106(2):756-63 (2005) (epub Apr. 7, 2005).
Hepatic disorders increasingly account for significant morbidity and mortality. Destruction of liver function by environmental and pathogenic causes presents significant public health risks to otherwise healthy individuals. Replacement of damaged or killed hepatocytes in such damaged organs is therefore a significant clinical goal. However, an ethically acceptable source for stem cells that can differentiate into hepatocytes remains unavailable. These and other unmet needs are provided herein.